Shibata Yasuyuki, Haruki Nobuhiro, Kuwabara Yoshiyuki, Ishiguro Hideyuki, Shinoda Noriyuki, Sato Atsushi, Kimura Masahiro, Koyama Hiroshi, Toyama Tatsuya, Nishiwaki Tadashi, Kudo Junzo, Terashita Yukio, Konishi Shigeru, Sugiura Hironori, Fujii Yoshitaka
Department of Surgery II, Nagoya City University Medical School, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Carcinogenesis. 2002 Oct;23(10):1695-9. doi: 10.1093/carcin/23.10.1695.
Cell cycle progression is monitored by checkpoint mechanisms to ensure the integrity of the genome and the fidelity of sister chromatid separation. Failure of such checkpoint functions results in genomic instability, a condition that predisposes cells to neoplastic transformation and tumor progression. Recently, Scolnick and Halazonetis defined a new mitotic checkpoint that acts at prophase and delays chromosome condensation in response to mitotic stress, and identified a gene, named checkpoint with FHA and ring finger (Chfr), that seems to be required for delaying prophase in human cells. In the present study, we examined human Chfr mRNA expression in 15 human esophageal cancer cell lines and 43 primary esophageal cancers to investigate the potential involvement of Chfr in the pathogenesis of esophageal cancers. We report here that a significant proportion of human esophageal cancer has loss of expression of Chfr gene. Furthermore, we found aberrant hypermethylation of the promoter region of this checkpoint gene in four of 15 (26.7%) esophageal cancer cell lines and in seven of 43 (16.3%) primary cancers.
细胞周期进程由检查点机制监控，以确保基因组的完整性和姐妹染色单体分离的准确性。这些检查点功能的缺失会导致基因组不稳定，这种情况使细胞易于发生肿瘤转化和肿瘤进展。最近，斯考尼克和哈拉佐内蒂斯定义了一种新的有丝分裂检查点，它在前期起作用，并在有丝分裂应激时延迟染色体浓缩，还鉴定出一个名为含FHA和环指结构域的检查点（Chfr）的基因，该基因似乎是人类细胞中延迟前期所必需的。在本研究中，我们检测了15种人类食管癌细胞系和43例原发性食管癌中人类Chfr mRNA的表达，以研究Chfr在食管癌发病机制中的潜在作用。我们在此报告，相当一部分人类食管癌存在Chfr基因表达缺失。此外，我们发现在15种（26.7%）食管癌细胞系中的4种以及43例原发性癌中的7例（16.3%）中，该检查点基因的启动子区域存在异常高甲基化。
